Electroporation is a basic technique in cellular and molecular biology largely used to introduce foreign molecules into cells by transient electrical permeabilization. Though commonly used in genetic engineering, it is not precise and it is difficult to optimize. The fundamental biophysics of the interaction between electrical potential and the permeabilization of the cell are not well understood. The basic hypothesis of this proposal is that during cell permeabilization, the electrical properties of a cell change in a measurable way. This change in properties can be detected through electrical measurements on the cell. The change in properties could be used: a) to study and control the process of electroporation and introduction of macromolecules into cells and b) to study the fundamental behavior of a cell membrane in an electrical field. Using micro-electromechanical techniques, the investigators will develop a chip that can incorporate a single cell in the electronic circuit of the chip, measure directly the electrical properties of the cell and electrically detect and control the permeabilization of the cell. The chip will be interfaced with a computer for controlled manipulation of cells. Using the new device and technology, the investigators will begin a study of the effect of electrical parameters on the process of permeabilization of a cell, to develop a fundamental understanding of the process of electroporation. The proposal is a technological invention that: a) could become an important research tool for developing a fundamental understanding of cell plasma membranes and the effect of the electrical potential on the membrane; and b) has practical applications in the biotechnology industry for controlled introduction of foreign molecules, such as plasmid vectors and drugs, into cells.